[Federal Register Volume 59, Number 12 (Wednesday, January 19, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-1154]
[[Page Unknown]]
[Federal Register: January 19, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 178
[Docket No. 90F-0257]
Indirect Food Additives: Adjuvants, Production Aids, and
Sanitizers
Agency: Food and Drug Administration, HHS.
Action: Final rule.
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Summary: The Food and Drug Administration (FDA) is amending the food
additive regulations to provide for the safe use of 3,5-di-tert-butyl-
4-hydroxyhydrocinnamic acid triester with 1,3,5-tris(2-hydroxyethyl)-s-
triazine-2,4,6-(1H,3H,5H)-trione as an antioxidant for polyester
elastomers in contact with dry food and rubber articles intended for
repeated use in contact with food. This action is in response to a
petition filed by the Ciba-Geigy Corp.
DATES: Effective January 19, 1994; written objections and requests for
a hearing by February 18, 1994.
Addresses: Submit written objections to the Dockets Management Branch
(HFA-305), Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr.,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Vir D. Anand, Center for Food Safety
and Applied Nutrition (HFS-216), Food and Drug Administration, 200 C
St. SW., Washington, DC 20204, 202-254-9500.
SUPPLEMENTARY INFORMATION: In a notice published in the Federal
Register of August 28, 1990 (55 FR 35188), FDA announced that a food
additive petition (FAP 0B4222) had been filed by Ciba-Geigy Corp.,
Seven Skyline Dr., Hawthorne, NY 10532-2188. The petition proposed that
Sec. 178.2010 Antioxidants and/or stabilizers for polymers (21 CFR
178.2010) be amended to provide for the safe use of 3,5-di-tert-butyl-
4-hydroxyhydrocinnamic acid triester with 1,3,5-tris(2-hydroxyethyl)-s-
triazine-2,4,6-(1H,3H,5H)-trione as an antioxidant for polyester
elastomers in contact with dry food and rubber articles intended for
repeated use in contact with food.
FDA, in its evaluation of the safety of this additive, reviewed the
safety of the additive and the chemical impurities that may be present
in the additive resulting from its manufacturing process. Although the
additive itself has not been shown to cause cancer, it has been found
to contain minute amounts of unreacted ethyl acrylate, a carcinogenic
reactant used in the manufacture of the additive. Residual amounts of
reactants and manufacturing aids, such as ethyl acrylate, are commonly
found as contaminants in chemical products, including food additives.
I. Determination of Safety
Under section 409(c)(3)(A) of the Federal Food, Drug, and Cosmetic
Act (the act) (21 U.S.C. 348(c)(3)(A), the so-called ``general safety
clause'' of the statute, a food additive cannot be approved for a
particular use unless a fair evaluation of the data available to FDA
establishes that the additive is safe for that use. FDA's food additive
regulations (21 CFR 170.3(i)) define ``safe'' as ``a reasonable
certainty in the minds of competent scientist that the substance is not
harmful under the intended conditions of use.''
The anticancer or Delaney clause (section 409(c)(3)(A) of the act)
further provides that no food additive shall be deemed safe if it is
found to induce cancer when ingested by man or animal. Importantly,
however, the Delaney clause applies to the additive itself and not to
impurities in the additive. That is, where an additive itself has not
been shown to cause cancer, but contains a carcinogenic impurity, the
additive is properly evaluated under the general safety clause using
risk assessment procedures to determine whether there is a reasonable
certainty that no harm will result from the proposed use of the
additive. Scott v. FDA, 728 F.2d 322 (6th Cir. 1984).
II. Safety of the Petitioned Use of the Additive
FDA estimates that the petitioned use of the additive 3,5-di-tert-
butyl-4-hydroxyhydrocinnamic acid triester with 1,3,5-tris(2-
hydroxyethyl)-s-triazine-2,4,6-(1H,3H,5H)-trione will result in
exposure to the additive of no greater than 100 parts per billion (ppb)
in the daily diet (Ref. 1).
FDA does not ordinarily consider chronic toxicological testing to
be necessary to determine the safety of an additive whose use will
result in such low exposure levels (Ref. 2), and the agency has not
required such testing here. However, the agency has reviewed the
available toxicological data from acute toxicity studies, subchronic
studies, and teratological studies on the additive. No adverse effects
were reported in these studies.
FDA has evaluated the safety of this additive under the general
safety clause, considering all available data and using risk assessment
procedures to estimate the upper-bound limit of risk presented by ethyl
acrylate, a carcinogenic chemical that may be present as an impurity in
the additive. This risk evaluation of the carcinogenic impurity ethyl
acrylate has two aspects: (1) Assessment of the exposure to the
impurity from the proposed use of the additive; and (2) extrapolation
of the risk observed in the animal bioassays to the conditions of
probable exposure to humans.
A. Ethyl Acrylate
Using risk assessment procedures, FDA has estimated the
hypothetical worst-case exposure to ethyl acrylate from the petitioned
use of the additive in the manufacture of polyester elastomers and
rubber articles for repeated use and currently regulated uses to be 380
parts per quadrillion of the daily diet (3 kilograms), or 1 nanogram
(ng) per person per day (Ref. 1). The agency used data from the
National Toxicology Program report (No. 259: 1986), a bioassay on ethyl
acrylate, to estimate the upper-bound limit of lifetime human risk from
exposure to this chemical stemming from the proposed use of the
additive and the level of ethyl acrylate that may be present in the
additive (Ref. 3). The results of the bioassay on ethyl acrylate
demonstrated that the material was carcinogenic for rats and mice under
the conditions of the study. The test material induced squamous cell
neoplasms in both sexes of F344/N rats and B6C3F1 mice when
administered by gavage in corn oil.
Based on the potential exposure of 1 ng per person per day, FDA
estimates that the upper-bound limit of individual lifetime risk from
the use of the 3,5-di-tert-butyl-4-hydroxyhydrocinnamic acid triester
with 1,3,5-tris(2-hydroxyethyl)-s-triazine-2,4,6-(1H,3H,5H)-trione is
8.1x10-11, or 8.1 in 100 billion (Ref. 4). Because of the numerous
conservatisms in the exposure estimate, the actual lifetime averaged
individual exposure to ethyl acrylate is expected to be substantially
less than the estimated daily intake, and therefore the calculated
upper-bound limit of risk would be less. Thus, the agency concludes
that there is a reasonable certainty that no harm from exposure to
ethyl acrylate would result from the proposed use of 3,5-di-tert-butyl-
4-hydroxyhydrocinnamic acid triester with 1,3,5-tris(2-hydroxyethyl)-s-
triazine-2,4,6-(1H,3H,5H)-trione.
B. Need for Specifications
The agency has also considered whether a specification is necessary
to control the amount of ethyl acrylate impurity in the food additive.
The agency finds that a specification is not necessary for the
following reasons: (1) Because of the low level at which ethyl acrylate
may be expected to remain as an impurity following production of the
additive, the agency would not expect this impurity to become a
component of food at other than extremely small levels; and (2) the
upper-bound limit of lifetime risk from exposure to this impurity, even
under worst-case assumptions, is very low, less than 8.1 in 100
billion.
C. Conclusion on Safety
FDA has evaluated data in the petition and other relevant material
and concludes that the proposed use of the additive in polyester
elastomers in contact with dry food and rubber articles intended for
repeated use in contact with food is safe. Based on this information,
the agency has also concluded that the additive will have the intended
technical effect. Therefore, Sec. 178.2010 should be amended as set
forth below.
In accordance with Sec. 171.1(h) (21 CFR 171.1(h)), the petition
and the documents that FDA considered and relied upon in reaching its
decision to approve the petition are available for inspection at the
Center for Food Safety and Applied Nutrition by appointment with the
information contact person listed above. As provided in 21 CFR
171.1(h), the agency will delete from the documents any materials that
are not available for public disclosure before making the documents
available for inspection.
III. Environmental Impact
The agency has carefully considered the potential environmental
effects of this action. FDA has concluded that the action will not have
a significant impact on the human environment, and that an
environmental impact statement is not required. The agency's finding of
no significant impact and the evidence supporting that finding,
contained in an environmental assessment, may be seen in the Dockets
Management Branch (address above) between 9 a.m. and 4 p.m., Monday
through Friday.
IV. Objections
Any person who will be adversely affected by this regulation may at
anytime on or before February 18, 1994, file with the Dockets
Management Branch (address above) written objection thereto. Each
objection shall be separately numbered, and each numbered objection
shall specify with particularity the provisions of the regulation to
which objection is made and the grounds for the objection. Each
numbered objection on which a hearing is requested shall specifically
so state. Failure to request a hearing for any particular objection
shall constitute a waiver of the right to a hearing on that objection.
Each numbered objection for which a hearing is requested shall include
a detailed description and analysis of the specific factual information
intended to be presented in support of the objection in the event that
a hearing is held. Failure to include such a description and analysis
for any particular objection shall constitute a waiver of the right to
a hearing on the objection. Three copies of all documents shall be
submitted and shall be identified with the docket number found in
brackets in the heading of this document. Any objection received in
response to the regulation may be seen in the Dockets Management Branch
between 9 a.m. and 4 p.m., Monday through Friday.
V. References
The following references have been placed on display in the Dockets
Management Branch (address above) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. Memorandum dated November 9, 1992, from the Food and Color
Additive Review Section (HFF-415), Indirect Additives Branch (HFF-
335), concerning FAP 0B4222 (Ciba-Geigy Corp.) exposure to the food
additive and its component (ethyl acrylate).
2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' in
Chemical Safety Regulation and Compliance, pp. 24-33, edited by F.
Homburger J. K. Marquis, and S. Karger, New York, NY, 1985.
3. ``Carcinogenesis Studies of Ethyl Acrylate (CAS Reg. No. 140-
88-5) in F-344/N Rats and B6C3F1 Mice'' (gavage studies),
National Toxicology Program, Technical Report Series, No. 259,
December 1986.
4. Memorandum dated April 19, 1993, from the Quantitative Risk
Assessment Committee, Center for Food Safety and Applied Nutrition,
concerning ethyl acrylate, FAP 0B4222.
List of Subjects in 21 CFR Part 178
Food additives, Food packaging.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
178 is amended as follows:
PART 178--INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND
SANITIZERS
1. The authority citation for 21 CFR part 178 continues to read as
follows:
Authority: Secs. 201, 402, 409, 721 of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 321, 342, 348, 379e).
2. Section 178.2010 is amended in the table in paragraph (b) for
the entry ``3,5-Di-tert-butyl-4-hydroxyhydrocinnamic acid triester with
1,3,5-tris(2-hydroxyethyl)-s-triazine-2,4,6-(1H,3H,5H)-trione'' by
numerically adding a new entry ``5'' under the heading ``Limitations''
to read as follows:
Sec. 178.2010 Antioxidants and/or stabilizers for polymers.
* * * * *
(b) * * *
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Substances Limitations
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*****
3,5-Di-tert-butyl-4- For use only:
hydroxyhydrocinnamic acid triester * * *
with 1,3,5-tris(2-hydroxyethyl)-s- 5. At levels not to exceed 2
triazine-2,4,6-(1H,3H,5H)-trione percent by weight of polyester
(CAS Reg. No. 34137-09-2). elastomers, complying with Sec.
177.1590 of this chapter, in
contact with dry food only, and
finished rubber articles for
repeated use, complying with Sec.
177.2600 of this chapter, in
contact with all foods, at
temperatures not to exceed 150
deg.F.
*****
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Dated: January 12, 1994.
Michael R. Taylor,
Deputy Commissioner for Policy.
[FR Doc. 94-1154 Filed 1-18-94; 8:45 am]
BILLING CODE 4160-01-F
